U.S. Pat. No. 4,602,092 to Thottathil et al discloses a method for preparing phosphinic acid intermediates having the structure ##STR9## wherein R is H or lower alkyl;
U.S. Pat. No. 4,337,201 to Petrillo discloses phosphinylalkanoyl substituted prolines which are angiotensin converting enzyme inhibitors, and have the formula ##STR15## and salts thereof, wherein
Included among the above compounds is fosinopril, that is ##STR22##
As described, the above phosphinylalkanoyl substituted prolines can be prepared by reacting a proline derivative having the formula ##STR23## wherein R.sub.4, is alkyl, arylalkyl or ##STR24## with a phosphinyl-acetic or propionic acid having the formula ##STR25## to form ##STR26## The reaction is accomplished using known amide bond forming procedures. For example, the reaction can be run in the presence of a coupling agent such as dicyclohexylcarbodiimide, or the above acid can be activated by formation of its mixed anhydride, symmetrical anhydride, acid halide (preferably acid chloride) or acid ester, or by the use of Woodward reagent K, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline, N,N'-carbonyldiimidazole or the like. A review of these methods can be found in Methoden der Organischem Chemie (Houben-Weyl), Vol. XV, part II, page 1 et seq. (1974).